Elsevier

JACC: Heart Failure

Volume 9, Issue 4, April 2021, Pages 254-264
JACC: Heart Failure

Focus Issue: Therapeutic Considerations
Clinical Research
Dapagliflozin in HFrEF Patients Treated With Mineralocorticoid Receptor Antagonists: An Analysis of DAPA-HF

https://doi.org/10.1016/j.jchf.2020.11.009Get rights and content
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Abstract

Objectives

The purpose of this study was to assess the efficacy and safety of dapagliflozin in patients taking or not taking an mineralocorticoid receptor antagonist (MRA) at baseline in the DAPA-HF (Dapagliflozin And Prevention of Adverse outcomes in Heart Failure) trial.

Background

MRAs and sodium glucose co-transporter 2 inhibitors each have diuretic activity, lower blood pressure, and reduce glomerular filtration rate (GFR). Therefore, it is important to investigate the safety, as well as efficacy, of their combination.

Methods

A total of 4,744 patients with heart failure with reduced ejection fraction (HFrEF) were randomized to placebo or dapagliflozin 10 mg daily. The efficacy of dapagliflozin on the primary composite outcome (cardiovascular death or episode of worsening heart failure) and its components was examined according to MRA use, as were predefined safety outcomes.

Results

A total of 3,370 patients (71%) were treated with an MRA and they were younger (65 vs. 69 years of age), less often from North America (9% vs. 26%), had worse New York Heart Association functional class (35% vs. 25% in class III/IV), lower left ventricular ejection fraction (30.7% vs. 31.9%) and systolic blood pressure (120.3 vs. 125.5 mm Hg), but higher estimated GFR (67.1 vs. 62.6 ml/min/1.73 m2), than patients not taking an MRA. The benefit of dapagliflozin compared with placebo was similar in patients taking or not taking an MRA: hazard ratio: 0.74 (95% confidence interval [CI]: 0.63 to 0.87) versus 0.74 (95% CI: 0.57 to 0.95), respectively, for the primary endpoint (p value for interaction = 0.97); similar findings were observed for secondary endpoints. In both MRA subgroups, safety outcomes were similar in patients randomized to dapagliflozin or placebo.

Conclusions

Dapagliflozin was similarly efficacious and safe in patients with HFrEF taking or not taking an MRA, supporting the use of both drugs together. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure [DAPA-HF]; NCT03036124)

Key Words

aldosterone
dapagliflozin
heart failure
hyperkalemia
kidney function
mineralocorticoid receptor antagonist
potassium
SGLT2 inhibitor

Abbreviations and Acronyms

CI
confidence interval
eGFR
estimated glomerular filtration rate
HF
heart failure
HFrEF
heart failure with reduced ejection fraction
HR
hazard ratio
LVEF
left ventricular ejection fraction
MRA
mineralocorticoid receptor antagonist
NT-proBNP
N-terminal pro–B-type natriuretic peptide
NYHA
New York Heart Association
SBP
systolic blood pressure
SGLT2
sodium glucose co-transporter 2

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